title: Dystroglycanopathies: coming into focus.
abstract: A common group of muscular dystrophies is associated with the aberrant glycosylation of α-dystroglycan. These clinically heterogeneous disorders, collectively termed dystroglycanopathies, are often associated with central nervous system and more rarely eye pathology. Defects in a total of eight putative and demonstrated glycosyltransferases or accessory proteins of glycosyltransferases have been shown to cause a dystroglycanopathy phenotype. In recent years the systematic analysis of large patient cohorts has uncovered a complex relationship between the underlying genetic defect and the resulting clinical phenotype. These studies have also drawn attention to the high proportion of patients that remain without a genetic diagnosis implicating novel genes in the pathogenesis of dystroglycanopathies. Recent glycomic analyses of α-dystroglycan have reported complex patterns of glycan composition and have uncovered novel glycan modifications. The exact glycan synthesis and modification pathways involved, as well as their role in ligand binding, remain only partially characterised. This review will focus on recent studies that have extended our knowledge of the mechanisms underlying dystroglycanopathies and have further characterised this patient population.
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health and the Great Ormond Street Hospital for Children, Guilford Street, University College London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Godfrey
authors.forename: A Reghan
authors.initials: AR
authors.lastname: Foley
authors.forename: Emma
authors.initials: E
authors.lastname: Clement
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000378:metabolism*; D005123:Eye / Q000378:metabolism / Q000473:pathology; D056726:Genetic Association Studies; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism*; D011134:Polysaccharides / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D011134:Polysaccharides; D049030:Dystroglycans; D016695:Glycosyltransferases